National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title

BRAIN Initiative: Optimization of
Transformative Technologies for Large Scale Recording and Modulation in the
Nervous System (U01 Clinical Trials Not Allowed)

Understanding the dynamic activity of neural circuits is
central to the NIH BRAIN Initiative. Although invention and proof-of-concept
testing of new technologies are a key component of the BRAIN Initiative, to
achieve their potential these technologies must also be optimized through
feedback from end-users in the context of the intended experimental use. This
FOA seeks applications for the optimization of existing and emerging technologies
and approaches that have potential to address major challenges associated
with recording and manipulating neural activity, at or near cellular
resolution, at multiple spatial and temporal scales, in any region and
throughout the entire depth of the brain. This FOA is intended for the
iterative refinement of emergent technologies and approaches that have
already demonstrated their transformative potential through initial
proof-of-concept testing, and are appropriate for accelerated development of
hardware and software while scaling manufacturing techniques towards
sustainable, broad dissemination and user-friendly incorporation into regular
neuroscience practice.

Proposed technologies should be compatible with
experiments in behaving animals, and should include advancements that enable
or reduce major barriers to hypothesis-driven experiments. Technologies
may engage diverse types of signaling beyond neuronal electrical activity for
large-scale analysis, and may utilize any modality such as optical,
electrical, magnetic, acoustic or genetic recording/manipulation.
Applications that seek to integrate multiple approaches are encouraged.
Applications are expected to integrate appropriate domains of expertise,
including where appropriate biological, chemical and physical sciences,
engineering, computational modeling and statistical analysis.

Key Dates

Posted Date

March 14, 2018

Open Date (Earliest Submission Date)

April 15, 2018

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

New Dates May 15, 2018, November 27, 2018, May 1, 2019, October 29, 2019, May 1, 2020, and October 29, 2020 , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

August 2018, January 2019, August 2019, January 2020,
August 2020, and January 2021

Advisory Council Review

January 2019, May 2019, January 2020, May 2020, January
2021, and May 2021

Earliest Start Date

February 2019, June 2019, February 2020, June 2020,
February 2021, June 2021

Expiration Date

October 30, 2020

Due Dates for E.O. 12372

Not Applicable

Required
Application Instructions

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and
Department of Health and Human Services partners. You must use one of these submission
options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online.

The Brain Research
through Advancing Innovative Neurotechnologies
(BRAIN) Initiative is aimed at revolutionizing our understanding of the human
brain. By accelerating the development and application of innovative
technologies, researchers will be able to produce a new dynamic picture of the
brain that, for the first time, will show how individual cells and complex
neural circuits interact in both time and space. It is expected that the
application of these new tools and technologies will ultimately lead to new
ways to treat and prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN
Initiative. Planning for the NIH component of the BRAIN initiative is guided by
the long-term scientific plan, "BRAIN 2025: A
Scientific Vision," which details seven high-priority research areas and
calls for a sustained federal commitment of $4.5 billion over 12 years. This
FOA and other recently issued FOAs are based on careful consideration by the
NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH
BRAIN Multi-Council Working Group. Videocasts of the NIH BRAIN Multi-council
Working Group are available at http://www.braininitiative.nih.gov/about/mcwg.htm.

In addition to the National BRAIN initiative, the NIH
continues to have a substantial annual investment in neuroscience research. The
Institutes and Centers contributing to the NIH BRAIN Initiative (http://braininitiative.nih.gov/)
support those research efforts through investigator-initiated applications as
well as through specific FOAs. Potential applicants to this FOA are strongly
encouraged to contact Scientific/Program staff if they have any questions about
the best FOA for their research.

To enable rapid progress in development of new technologies
as well as in theory and data analysis, the BRAIN Initiative encourages
collaborations between neurobiologists and scientists from statistics, physics,
mathematics, engineering, and computer and information sciences; and NIH
welcomes applications from investigators in these disciplines.

The BRAIN Initiative will require a high level of
coordination and sharing between investigators. It is expected that BRAIN
Initiative awardees will cooperate and coordinate their activities after awards
are made by participating in Program Director/Principal Investigator (PD/PI)
meetings and in other activities.

Objectives

This FOA is related to the recommendations in section III of
the BRAIN 2025 Report, with the goal to 'produce a dynamic picture of the
functioning brain by developing and applying improved methods for large-scale
monitoring of neural activity'. Towards this end, the report calls for
accelerated development of new and improved electrodes for large-scale
recording, new and improved electrical and chemical optical sensors of neural
activity, and new and improved instruments for optical monitoring of neural
activity. These new technologies and approaches will provide unprecedented
opportunities for exploring how the nervous system encodes, processes,
utilizes, stores, and retrieves vast quantities of information. A better
understanding of this dynamic neural activity will enable researchers to seek
new ways to diagnose, treat, and prevent brain disorders.

This FOA also addresses a core principle of the BRAIN 2025
report: to critically test and further develop new methods through iterative
interaction between technologists and experimentalists with a goal of broad
dissemination and integration into regular neuroscience practice.

This FOA seeks applications for the optimization of existing
and emerging technologies and approaches for large-scale recording and
manipulation of neural activity, to enable transformative understanding of
dynamic signaling in the nervous system.

This FOA is intended for the iterative refinement of
emergent technologies and approaches that have already demonstrated their
transformative potential through initial proof-of-concept testing, and are
appropriate for accelerated engineering development while scaling manufacturing
techniques towards sustainable, broad dissemination and incorporation into
regular neuroscience practice.

An additional FOA (RFA-NS-18-020)
solicits applications for proof-of-concept testing and development of new
technologies and novel approaches for large-scale recording and manipulation of
neural activity.

Applications are expected to address any or all of the
following three general goals for the FOA:

1.
Develop New Large-Scale Network Recording Capabilities.

Recording dynamic neural activity from complete neural
networks, over long periods, in any area of the brain is a challenging but
essential goal. Advances in the exploration and development of new
technologies for neural cell recording, including methods based on electrodes,
microelectronics/microchips, imaging, molecular genetics, and nanoscience are
encouraged. It is expected that progress will initially be tractable in
non-human animals (invertebrate or vertebrate), but extrapolation to human
circuits is an ultimate goal.

2.
Develop Tools for Circuit Manipulation.

The ability to activate and inhibit specific populations of
neurons is key to understanding functional circuits, which will advance the
scope of our knowledge from observation of neural phenomena to a mechanistic
understanding of neural causation. A new generation of tools for optogenetics,
pharmacogenetics, biochemical, electromagnetic and/or acoustic modulation needs
to be developed for use in animals, and eventually in humans, to enable the
immense potential of circuit manipulation.

3.
Link Neural Activity to Behavior.

The goal of this FOA is to produce technologies with
potential to elucidate nervous system function, in health and disease, in the
context of complex behaviors. Proposed technologies should be compatible with
experiments in behaving animals and should be validated under in vivo
experimental conditions. In addition, novel approaches for enabling
large-scale neural recording or manipulation during complex behaviors are
encouraged along with the computational and statistical tools necessary to link
neural activity to behavior. In combination with concurrent measurement and
manipulation of neuronal activity, applications may propose methods to enhance
the ability to quantify and interpret animal behavior, at high temporal and
spatial resolution, reliably and objectively, over long periods of time and
under a broad set of conditions.

Applications
submitted in response to this FOA should address the following considerations:

This FOA is for the optimization of existing and emerging
technologies and approaches with the potential to address major challenges
associated with recording and manipulating neural activity, at or near cellular
resolution, at multiple spatial and temporal scales, in any region and
throughout the entire depth of the brain.

The proposed technologies should enable hypothesis-driven
experiments that are currently infeasible, or reduce barriers to experiments
that currently are costly, difficult, or take too long to perform.

Proposed technologies should be compatible with experiments in
behaving animals, and should increase the spatial and/or temporal scale of
current methods, while minimizing the loss of cellular/sub-cellular and
temporal resolution.

Applications may utilize experimental recording and manipulating
techniques of any modality, such as optical, electrical, magnetic, acoustic or
genetic recording/manipulation.

Applications that seek to integrate multiple technical and
experimental approaches are encouraged.

Applicants should note that crossing boundaries in
interdisciplinary collaborations is a major goal of the BRAIN Initiative.
Accordingly, applicants are strongly encouraged to consider, where appropriate,
multi-PD/PI applications that integrate various domains of expertise, including
biological, chemical and physical sciences, engineering, computational modeling
and statistical analysis.

The following types of approaches are encouraged. Each
bullet includes representative, but not exhaustive, examples.

Probes for resolving changes in membrane potential, with high
spatial and temporal resolution, from large numbers of neurons in behaving
animals.

Probes for sampling or manipulating activity over a range of
spatial and temporal scales in the same experiment, or for large-scale
sampling/manipulation of cellular activity with simultaneous whole-brain
activity measurements.

Probes for recording/manipulating diverse cell types
simultaneously, with distinguishable readouts and interventions (e.g., probes
responsive to different ranges of the energy spectrum).

Probes for neural plasticity events, at the cellular or synaptic
level (including genetic and epigenetic events), which underlie network
adaptation and learning.

Probes for cellular or network modulatory states (e.g., as
assessed by intracellular signaling cascades, or modulatory transmitter
levels), which are major determinants of cellular and network responses to
incoming information.

Probes for signaling at specific sets of nerve terminals, or by
specific neurotransmitters with synaptic resolution, especially
techniques/approaches that distinguish transmitters or classes of synapses from
one another.

Optical imaging instrumentation with major increases in
large-scale sampling capabilities, including frame rates sufficient to capture
millisecond-scale signaling events, across full volumes of neural tissue rather
than single focal planes.

New imaging modalities for less-invasive or non-invasive
cellular-resolution imaging at tissue depths that are currently unavailable,
such as structured imaging or adaptive strategies using spatial light
modulation and/or wavefront sensing, photoacoustic wavefront shaping,
backscattering and deconvolution strategies, or signal relay approaches.

In combination with concurrent development of large-scale
technology for recording/manipulation, computational and statistical tools to
analyze and model neural circuit activity underlying behavior and/or to affect
systems of behavior.

This FOA is milestone-driven and involves NIH program
staff's participation in developing the project plan, monitoring the progress,
and making go/no-go decisions.

Applicants are strongly encouraged to consult the
Scientific/Research Contact listed below to discuss the alignment of their
proposed work with the goals of this FOA, and the BRAIN Initiative Program.

Cooperative Agreement: A support
mechanism used when there will be substantial Federal scientific or
programmatic involvement. Substantial involvement means that, after award,
NIH scientific or program staff will assist, guide, coordinate, or
participate in project activities. See Section VI.2 for additional
information about the substantial involvement for this FOA.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Clinical Trial?

Not Allowed: Only accepting applications that do not
propose clinical trials

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to
apply.
Foreign components, as defined in
the NIH Grants Policy Statement, are allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping
applications under review at the same time. This means that the NIH will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application
pending appeal of initial peer review (see NOT-OD-11-101).

Section IV. Application and Submission Information

1. Requesting an
Application Package

Buttons to access the online ASSIST system or to download
application forms are available in Part
1 of this FOA. See your administrative office for instructions if you plan
to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed. Applications should include a plan for ongoing consultation
with end users, relevant expert technologists, and where applicable, experts in
appropriate manufacturing technologies for sustainable dissemination.
Named individuals from these groups who will serve as consultants for the
project are encouraged.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed. The budget should include funds necessary for travel for up
to two key personnel to participate in a BRAIN investigator meeting, lasting
not more than two days and including up to two overnight stays, for each year
of the project.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

It is anticipated that many projects will begin with a
limited roll-out to selected user-groups to provide iterative feedback and
further refine requirements in the context of conducting model experiments, as
well as metric-driven validation of the technology in comparison to current
best practices, where appropriate. Although proposed technologies will
enable or reduce major barriers to hypothesis-driven experiments, applications must
focus on the technology rather than experimental or biological aims. The
experiments described should be formulated to validate the technology and
demonstrate its capabilities, rather than advancing the state of biological
knowledge. Applicants are expected to explain the specific biological
assay(s) to be utilized for validation.

As applications are expected to have demonstrated basic
proof-of-concept for the technology prior to entry, applications will in part
be evaluated by providing a clear, comprehensive, and credible path towards
transitioning an emerging technology to broad and routine neuroscience
practice. Consequently, applications must provide a strategy to develop
the technology towards reliable, sustainable manufacture suitable for broad
dissemination and integration into regular neuroscience practice.

All applications should include the following:

Current
State-of-the-Art: Investigators should specifically define the
current state of technology as a benchmark against which their proposed
improvements will be measured.

Milestones
and Timeline: Applications must propose annual milestones that
represent verifiable go/no-go criteria for continued funding. Milestones
will be agreed upon at the start of each project, and milestone progress should
be included by investigators in each annual progress report. If a funded
project does not make sufficient progress toward the agreed-upon milestones at
any stage, funding for the project may be decreased or discontinued.

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

A central goal of this FOA is to further advance research by
generating transformative tools and technologies that will be widely used
throughout the research community. Applications are expected to include a
detailed plan for dissemination and sustainability of proposed resources,
consistent with achieving the goals of this program.

Dissemination plans should include the following key
elements:

Project management of resource sharing or dissemination;

Description of the specific resources to be shared;

Milestones with schedule for availability and for breadth of
dissemination;

Persons who will have access to the resources (written as broadly
as possible to the extent consistent with applicable laws, regulations, rules,
and policies);

Plan for post award disposition of resources. It is
expected that preference will be given towards eventual commercial manufacture,
although plans with an end-goal of future dissemination capitalizing on
existing NIH or alternate funding agency funding mechanisms will be considered.

Appendix:

Only limited Appendix materials are allowed. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical
research, and/or clinical trials (and when applicable, clinical trials research
experience) follow all instructions for the PHS Human Subjects and Clinical
Trials Information form in the SF424 (R&R) Application Guide, with the
following additional instructions:

If you answered "Yes" to the question "Are Human Subjects
Involved?" on the R&R Other Project Information form, you must include at
least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials
Information form or Delayed
Onset Study record.

Study
Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide
must be followed

Delayed
Onset Study

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide
must be followed.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH
Grants Policy Statement, and procedures for foreign institutions.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), NATO
Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and
Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission. When
a submission date falls on a weekend or Federal
holiday, the application deadline is automatically extended to the next
business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date and time. If a Changed/Corrected application is submitted after the
deadline, the application will be considered late. Applications that miss the
due date and time are subjected to the NIH Policy on Late Application
Submission.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically. If you encounter a system issue beyond your control that
threatens your ability to complete the submission process on-time, you must
follow the Guidelines
for Applicants Experiencing System Issues. For assistance with application
submission, contact the Application Submission Contacts in Section VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization's profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness and compliance with application instructions by the Center for
Scientific Review and responsiveness by components
of participating organizations, NIH. Applications that are incomplete, non-compliant
and/or nonresponsive will not be reviewed.

Applications
Involving the NIH Intramural Research Program

The requests by NIH Intramural Scientists will be limited to
the incremental costs required for participation. As such, these requests will
not include any salary and related fringe benefits for career, career
conditional or other Federal employees (civilian or uniformed service) with
permanent appointments under existing position ceilings or any costs related to
administrative or facilities support (equivalent to Facilities and
Administrative or F&A costs). These costs may include salary for staff to
be specifically hired under a temporary appointment for the project, consultant
costs, equipment, supplies, travel, and other items typically listed under
Other Expenses. Applicants should indicate the number of person-months devoted
to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH
Intramural Program. NIH intramural scientists will participate in this program
as PDs/PIs in accord with the Terms and Conditions provided in this FOA.
Intellectual property will be managed in accord with established policy of the
NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent
rights for inventions developed in NIH facilities are NIH property unless NIH
waives its rights.

Should an extramural application include the collaboration
with an intramural scientist, no funds for the support of the intramural
scientist may be requested in the application. The intramural scientist may
submit a separate request for intramural funding as described above.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in the policy.
Any instructions provided here are in addition to the instructions in the
policy.

Section V. Application Review Information

Important Update: See NOT-OD-18-228 for updated review language
for due dates on or after January 25, 2019.

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following:

This FOA is for the optimization of existing and emerging
technologies and approaches. As proof-of-concept is required prior
to entry, innovation will in part be evaluated by having a clear,
comprehensive, and credible path towards transitioning an emerging technology
to broad and routine neuroscience practice. It is expected that applications
will incorporate design requirements from end-users, and clear, quantifiable
performance metrics that incorporate the end-use experience.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an
important problem or a critical barrier to progress in the field? Is there a
strong scientific premise for the project? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Does the proposed technology
represent a major improvement over current state-of-the-art? Will it
serve to enable hypothesis-driven experiments that are currently infeasible, or
reduce major barriers to experiments that currently are costly, difficult, or
take too long to perform?

Investigator(s)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or those in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Innovation

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy,
methodology, and analyses well-reasoned and appropriate to accomplish the
specific aims of the project? Have the investigators presented strategies to
ensure a robust and unbiased approach, as appropriate for the work proposed? Are
potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed? Have
the investigators presented adequate plans to address relevant biological
variables, such as sex, for studies in vertebrate animals or human subjects?

Is the overall plan for iterative
development well staged, tractable and appropriately adaptive? Are
initial design criteria proposed with clear and justifiable metrics for
verification and validation? Were these initial design criteria developed
through appropriate communication with end-users? Are the experiments
formulated to validate the technology and demonstrate its capabilities, rather
than advancing the state of biological knowledge? Are there proposed
development milestones that are adequate, measurable and feasible?

If the project involves human
subjects and/or NIH-defined clinical research, are the plans to address 1) the
protection of human subjects from research risks, and 2) inclusion (or
exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as
well as the inclusion or exclusion of children, justified in terms of the
scientific goals and research strategy proposed?

Environment

Will the scientific environment in
which the work will be done contribute to the probability of success? Are the
institutional support, equipment and other physical resources available to the
investigators adequate for the project proposed? Will the project benefit from
unique features of the scientific environment, subject populations, or
collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human
subjects but does not involve one of the six categories of research that are
exempt under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate: 1)
the justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion of Women, Minorities,
and Children

When the proposed project involves
human subjects and/or NIH-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of children to determine if it is justified in terms of the
scientific goals and research strategy proposed. For additional information on
review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the
project presents special opportunities for furthering research programs through
the use of unusual talent, resources, populations, or environmental conditions
that exist in other countries and either are not readily available in the
United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the
information provided in this section of the application, including 1) the
Select Agent(s) to be used in the proposed research, 2) the registration status
of all entities where Select Agent(s) will be used, 3) the procedures that will
be used to monitor possession use and transfer of Select Agent(s), and 4) plans
for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Is there a convincing path towards a sustainable
product for wide dissemination as appropriate and consistent with achieving the
goals of the program? Reviewers should evaluate the resource sharing plan
focusing on the following elements:

Project
management of resource sharing or dissemination;

Description
of the specific resources to be shared;

Milestones
with schedule for availability and for breadth of dissemination;

Persons
who will have access to the resources (written as broadly as possible to the extent
consistent with applicable laws, regulations, rules, and policies);

Plan for post award disposition of resources.
It is expected that preference will be given towards eventual commercial
manufacture, although plans with an end-goal of future dissemination
capitalizing on existing NIH or alternate funding agency funding mechanisms
will be considered.

Authentication of Key Biological
and/or Chemical Resources:

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by NINDS, in accordance
with NIH
peer review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response
to this FOA.

Applications will be assigned to the appropriate NIH
Institute or Center. Applications will compete for available funds with all
other recommended applications submitted in response to this FOA. Following
initial peer review, recommended applications will receive a second level of
review by the National Advisory Neurological Disorders and Stroke Council. The
following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons. Refer to Part 1 for dates for peer review, advisory council
review, and earliest start date.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be
subject to terms and conditions found on the Award
Conditions and Information for NIH Grants website. This includes any
recent legislation and policy applicable to awards that is highlighted on this
website.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person's race, color, national
origin, disability, age and, in some circumstances, sex and religion. This
includes ensuring your programs are accessible to persons with limited English
proficiency. HHS recognizes that research projects are often limited in scope
for many reasons that are nondiscriminatory, such as the principal
investigator's scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

In accordance with the statutory provisions contained in
Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal
Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal
Awardee Performance and Integrity Information System (FAPIIS) requirements.
FAPIIS requires Federal award making officials to review and consider
information about an applicant in the designated integrity and performance
system (currently FAPIIS) prior to making an award. An applicant, at its
option, may review information in the designated integrity and performance
systems accessible through FAPIIS and comment on any information about itself
that a Federal agency previously entered and is currently in FAPIIS. The
Federal awarding agency will consider any comments by the applicant, in
addition to other information in FAPIIS, in making a judgement about the
applicant's integrity, business ethics, and record of performance under Federal
awards when completing the review of risk posed by applicants as described in
45 CFR Part 75.205 "Federal awarding agency review of risk posed by applicants."
This provision will apply to all NIH grants and cooperative agreements except
fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this
program will be the cooperative agreement, an "assistance" mechanism
(rather than an "acquisition" mechanism), in which substantial NIH
programmatic involvement with the awardees is anticipated during the
performance of the activities. Under the cooperative agreement, the NIH purpose
is to support and stimulate the recipients' activities by involvement in and
otherwise working jointly with the award recipients in a partnership role; it
is not to assume direction, prime responsibility, or a dominant role in the
activities. Consistent with this concept, the dominant role and prime
responsibility resides with the awardees for the project as a whole, although
specific tasks and activities may be shared among the awardees and the NIH as
defined below.

Attending meetings with investigators, BRAIN Initiative staff
and/or leadership, and members of the BRAIN Initiative Multi-Council Working
Group to foster collaborations and exchange information and ideas to accelerate
progress towards the goals of the BRAIN Initiative.

Developing milestones with specific timelines and criteria for
evaluation, and making appropriate revisions based on the feedback from the
Principal Investigator meetings and recommendations from the Program Officer
and/or Project Team.

Discussing and sharing information, preliminary results, raw
data, resources and technology with the Program Officer and/or Project Team and
the other investigative teams (i.e., recipients of awards issued under this
FOA) as appropriate and consistent with achieving the goals of the BRAIN
Initiative.

Sharing data, final results and technology with the broader
research community as appropriate and consistent with achieving the goals of
the program.

NIH
staff have substantial programmatic involvement that is above and beyond the
normal stewardship role in awards, as described below:

A Program Officer will be assigned to this award. The
Program Officer will be responsible for normal scientific and programmatic
stewardship and guidance.

A group of NIH program staff from the ICs contributing to the NIH
BRAIN Initiative will form a Project Team for this award. The Project
Team will review annual progress reports and other documents from the awardees
and will assist the Program Officer in the evaluation of progress and
coordination of activities with other awardees under this FOA.

One or more extramural NIH program staff member will be assigned
as the Project Coordinator for each award under this FOA. The same person
may serve as the Project Coordinator for multiple BRAIN Initiative
awards. The Project Coordinator(s) will also be a member of the Project
Team.

The Project Coordinator is not involved with normal program
stewardship, but will provide technical assistance, advice, coordination, and
other program actions supporting the recipients of these cooperative agreements
during the conduct of an activity, which may be above and beyond the levels
required normally for program stewardship of grants.

The additional duties of the Project Coordinator may include
attending and participating in meetings of Principle Investigators and NIH
Staff, assisting in the development of the meeting agendas, assisting in
evaluating achievement of milestones, assisting with the establishment of a
consortium for the purpose of sharing information and coordination of research
activities among the recipients of these cooperative agreements.

Areas
of Joint Responsibility include:

Establishing a Scientific Steering Committee to provide guidance
and feedback on strategic priorities and technology optimization for eventual
reliable, sustainable manufacture suitable for broad dissemination and
integration into regular neuroscience practice. The committee should include at
least three established researchers with relevant technical and scientific
expertise. Specific committee members should not be named in the grant
application and membership will be negotiated with program staff at the time of
award. At least two meetings per year should be planned. NIH program staff are
required to be invited to all steering committee meetings.

Dispute
Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that is
otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart
D and DHHS regulation 45 CFR Part 16.

A final RPPR, invention statement,
and the expenditure data portion of the Federal Financial Report are required for
closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

In accordance with the regulatory requirements provided at
45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have
currently active Federal grants, cooperative agreements, and procurement
contracts from all Federal awarding agencies with a cumulative total value
greater than $10,000,000 for any period of time during the period of
performance of a Federal award, must report and maintain the currency of
information reported in the System for Award Management (SAM) about civil,
criminal, and administrative proceedings in connection with the award or
performance of a Federal award that reached final disposition within the most
recent five-year period. The recipient must also make semiannual
disclosures regarding such proceedings. Proceedings information will be
made publicly available in the designated integrity and performance system
(currently FAPIIS). This is a statutory requirement under section 872 of
Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010
of Public Law 111-212, all information posted in the designated integrity and
performance system on or after April 15, 2011, except past performance reviews
required for Federal procurement contracts, will be publicly available. Full
reporting requirements and procedures are found in Appendix XII to 45 CFR Part
75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.